PB1867: ACUTE MYELOID LEUKEMIA WITH MUTATED NPM1 – REAL-LIFE EXPERIENCE IN THE REDEFINITION OF EUROPEAN LEUKEMIANET RISK CLASSIFICATION
Authors: Rita S Gomes, Pedro Amorim Machado, Adriana Roque, Margarida Coucelo, Teresa Simões, Ana Oliveira, Telma Nascimento, Sandra Marini, Marta Pereira, Emilia Cortesão
Journal: HemaSphere (2023)

Topic: 4. Acute myeloid leukemia - Clinical Background: Acute myeloid leukemia (AML) with mutated Nucleophosmin-1 (NPM1) usually carries a better prognosis, being associated with favorable response to standard intensive chemotherapy (IC). However, the impact of additional molecular and cytogenetic alterations on prognosis, incited a redefining of AML risk classification by the European LeukemiaNet (ELN). Aims: To compare the prognostic impact of ELN2017 and ENL2022 in a real-life cohort. Methods: Retrospective, single-centre study of 41 AML-NPM1 pts diagnosed between jan/2015 and jul/2022. Clinical, cytogenetic and molecular data at diagnosis were analyzed. Prognostic risk was determined according to ELN2017 and ELN2022. Pts that did not had available data to score ELN models (n=5) were excluded from the global analysis and pts that did not received IC (n=11) were excluded from response and survival outcomes analysis. The inter-score classification concordance was evaluated by Cohen’s kappa test. Stratified models for each of the ELN risk classifications were compared using Akaike’s information criterion (AIC) and the Harrell’s concordance index (C-index). A p-value<0.05 was considered statistically significant. Results: We included 36 pts, 44% male, with a median age of 61 years (22-79). Median variant allele frequency (VAF) in evaluable patients (n=17) was 44% (11-55). Considering conventional cytogenetics, 44% had normal karyotype and 17% had complex karyotype. Concerning molecular alterations, 15 (42%) was FLT3-ITD (7/15 [47%] with high allelic ratio [≥0.5]). Among 16 cases with NGS (Next Generation Sequencing) panel, 11 (65%) had ≥2 mutations, 7 (41%) had DNMT3A and 5 (29%) had TET2 mutations. Considering ELN2017, 23 (64%) pts were classified has favorable (FR), 6 (17%) as intermediate (IR) and 7 (19%) as adverse risk (AR). Considering ELN2022, 15 (42%) pts were classified has FR, 14 (39%) as IR and 7 (19%) as AR. The concordance between both scores was substantial (agreement 77.8%; kappa 0.6479;p<0.001). However, 8 (35%) pts classified as FR by ELN2017 were re-classified as IR by ELN2022.Twenty-two pts (61%) received IC (4 of whom also received midostaurin), 2 (6%) received hypomethylating agents and the remaining received only palliative support or died before any therapeutics. Considering eligible pts for outcome analysis (n=25), 20/22 (91%) attained complete morphologic remission (CR) and 15/21 (71%) had negative MFC-MRD (multi-color flow-cytometry – minimal residual disease) after induction therapy. Five pts (14%) were submitted to allogeneic stem cell transplantation. The median overall survival (OS) was 33.5 months. Neither ELN2017 nor ELN2022 predicted significantly different 2-years OS between risk groups (p=0.3423 and p=0.775, respectively). ELN2017 discriminated best between patients with poor and favorable OS than ELN2022 (indicated by the lowest AIC value [146.8 and 146.9] and the highest C-index [0.5399 and 0.5213], respectively). However, the differences between the indexes are small and both exhibited a fair discrimination between short and long survival times. Summary/Conclusion: In our cohort neither ELN2017 nor ELN2022 was better in predicting survival and did not establish significant survival differences between risk groups, probably due to the small sample size. An important number of patients classified as FR in ELN2017 were reclassified in higher risk strata with ELN2022. Therefore, the latter may impact therapeutic strategies in a subgroup of pts. Keywords: Acute myeloid leukemia, Prognosis, Progenitor cell